Mannose-binding lectin (MBL) plays an important role in the innate immune response via its ability to recognize sugar moieties on the surfaces of a great variety of pathogens. MBL binding leads to destruction by opsonization and/or activation of the complement pathway in an antibody-independent manner. Thus, MBL deficiency has been associated with numerous immune-related diseases including rheumatoid arthritis, systemic lupus erythematosus, and severe infections in children and immunocompromised adults. In addition, the progression of several diseases, including cystic fibrosis, hepatitis BIC and HIV, are also associated with MBL expression. The transcription and functional activity of MBL depend upon polymorphisms within the gene and their phase or haplotypic configuration. Therefore, the ability to easily and inexpensively determine an individual's MBL haplotype would help establish a stronger link between MBL and disease susceptibility and progression, and aid in the development of a diagnostic test. This Phase I proposal applies PolyGenyx's novel molecular SNP haplotyping approach to developing a highthroughput assay for 12 polymorphisms within the MBL gene. Currently, no other method allows simple, reliable, accurate high-throughput haplotyping of SNP loci. Phase II studies are expected to associate an individual's MBL haplotype with risk of infection. Due to the wide variety of diseases influenced by MBL, the potential commercial applications for a haplotyping assay are diverse and economically attractive. For instance, the annual economic impact of rheumatoid arthritis is estimated at $15B in direct medical costs and $60B in indirect costs. For each disease, evaluating the patient's MBL status would be extremely beneficial. Patients with a haplotypic configuration predicting increased risk of disease/infection could undergo several steps to reduce this risk, improve their quality of life, and reduce the total economic impact to society.